Diabetic kidney disease(DKD)is a high incidence microvascular complication caused by diabetes mellitus(DM).Persistent high glucose induces oxidative stress in the body.nuclear factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1)can play an anti-inflammatory and anti-oxidative role by inhibiting the accumulation of extracellular matrix in glomerular mesangium,inhibiting epithelial-mesenchymal transition in renal tubular epithelial cells,and inhibiting iron apoptosis,so as to improve renal function damage and delay the process of DKD.This article reviews the relationship between Nrf2/HO-1 pathway and DKD and the effect of traditional Chinese medicine active ingredients on DKD through Nrf2/HO-1 signaling pathway,in order to provide a basis for the development of new drugs.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant solid tumor of the digestive system, characterized by rapid progression and difficulties of early diagnosis. Five-year survival rate of the patients is less than 9%. With the acceleration of global population aging and lifestyle change, the incidence of PDAC has been increasing annually. Currently, surgical treatment and chemotherapy remain the standard treatment options for PDAC patients. Early symptoms of PDAC are so undetectable that most patients miss the optimal opportunity for radical surgical resection. Even among those who undergo surgery, the high recurrence rate remains a major problem. PDAC is known for its unique tumor microenvironment. The cellular and non-cellular components in the tumor microenvironment account for as much as 90% of the tumor stroma, presenting many potential targets for PDAC therapy. Activated pancreatic stellate cells within PDAC tissue express specific proteins and secrete various cytokines and metabolites, which directly contribute to the proliferation, invasion, and metastasis of PDAC cells. These elements are critical in extracellular matrix production, connective tissue hyperplasia, immune tolerance, and drug resistance. Immune cells, such as macrophages and neutrophils, exert immunosuppressive and tumor-promoting roles in PDAC progression. The extracellular matrix, which serve as a natural physical barrier, induces interstitial hypertension and reduces blood supply, thereby hindering the delivery of drugs to the tumor. Additionally, it helps the metastasis and differentiation of PDAC cells, reducing the efficacy of clinical chemotherapy and immunotherapy. Although chemotherapeutic agents like gemcitabine have been used in the clinical treatment of PDAC for more than 20 years, the curative effect is obstructed by their poor stability in the bloodstream, low cellular uptake, and poor targeting. While small-molecule inhibitors targeting mutations such as KRAS^G12C, BRCA, and NTRK fusion have shown great potential for molecular targeted treatments and gene therapies of PDAC, their broader application is limited by side effects and restricted scope of patients. The advancement of nanotechnology brings new strategies for PDAC treatment. By virtue of unique size characteristics and actual versatility, different drug-delivery nanosystems contribute to overcome the dense stromal barrier, prolong the circulation time of therapeutics and realize precise PDAC treatment by targeted drug delivery. Clinical nanodrugs such as albumin-bound paclitaxel (nab-paclitaxel) and irinotecan liposome greatly improve the pharmacokinetics of conventional chemotherapeutics and promote drug accumulation inside the tumor, thereby are applying to the first-line treatment of PDAC. It is noteworthy that none nanodrugs with active targeting design have been approved for clinical treatment yet, though many are in clinical trials. In this review, we discuss promising targeting strategies based on different nanodrug delivery systems for treatment of PDAC. One major nanostrategy focuses on the tumor cell targeting and its applications in chemotherapy, molecular targeting therapy, gene therapy, and immunotherapy of PDAC. Another nanostrategy targets the tumor microenvironment, which highlights the nanosystems specifically regulating pancreatic stellate cells, immune cells and the extracellular matrix. Recent progress of developing new nanotheraputics for breakthrough in the fight of PDAC are elaborated in this review. We also provide our perspectives on the challenges and opportunities in the field.

The theoretical foundations of the forward and inverse problems of two conductivity imaging methods based on magneto-acoustic coupling effects,including magneto-acoustic tomography(MAT)and magneto-acousto-electrical tomogra-phy(MAET),were introduced.The research progress of the conductivity reconstruction methods with different imaging strate-gies was reviewed.The problems of the conductivity reconstruction methods based on magnetoacoustic coupling effects were analyzed in terms of acoustic source model construction,reconstruction algorithm and imaging speed,and the future develop-ment directions were pointed out.[Chinese Medical Equipment Journal,2024,45(7):94-104]

AIM:To investigate the effects and underlying mechanism of Toona sinensis bark extract(TAE)on the colon mucosal barrier and gut microbiota in mice with ulcerative colitis(UC)induced by dextran sulfate sodium(DSS).METHODS:Sixty C57BL/6J mice were randomly assigned to control,model,and mesalazine(0.2 g/kg)groups,as well as TAE groups(low,medium,and high-doses equal to crude drug concentrations of 2.3,4.6 and 9.2 g/kg,respectively).The UC model was induced by drinking of 2.5％DSS,and mean while the drugs were administered for 10 days.The mice were then evaluated in terms of weight,disease activity index(DAI),colon length,spleen index,and pathological changes in the colon tissues.In addition,the level of apoptosis in colon tissues was assessed by terminal de-oxynucleotidyl transferase dUTP nick-end labeling(TUNEL)fluorescence staining,and the expression of related proteins was evaluated by Western blot,levels of inflammatory factors were determined by enzyme-linked immunosorbent assays(ELISA),and the activities of total superoxide dismutase(T-SOD)and catalase(CAT)and malondialdehyde(MDA)content were assessed by biochemical assays.Furthermore,the constitution and diversity of the gut microbiota were inves-tigated by 16S rRNA gene sequencing.RESULTS:Compared with the control group,mice in the model group showed significantly reduced body weights(P<0.01),and the colon length was shortened significantly(P<0.05).Marked in-creases in the DAI and spleen index were observed(P<0.01),along with severe damage to the colon mucosa(P<0.01).Mechanistically,the level of intestinal epithelial cell apoptosis was significantly raised(P<0.01).The model group showed markedly reduced expression of occludin and claudin-1(P<0.01),the level of IL-10,and activities of T-SOD and CAT in the colon tissues(P<0.01).While the levels of IL-6,IL-1β,TNF-α,and the MDA content were increased signif-icantly(P<0.05).The abundance and diversity of the gut microbiota were decreased in the model group(P<0.05).Com-pared with the model group,all these indicators were ameliorated by the administration of TAE(P<0.05).The abundance of pathogenic bacteria,including Proteobacteria and Escherichia-Shigella,was decreased remarkably(P<0.05),while that of probiotics,including Bacteroidota and Muribaculaceae,were increased significantly(P<0.05).The abundance and diversity of the gut microbiota were increased.CONCLUSION:Taken together,Toona sinensis bark alcohol extract can alleviate damage to the intestinal mucosa by suppressing the apoptosis of intestinal epithelial cell,reducing the inflam-matory response,and mitigating oxidative stress.Treatment with TAE could also maintain the homeostasis of the gut micro-biota by regulating the abundance,ultimately meliorate the function of intestinal mucosal barrier.

Objective To investigate the efficacy and safety of a new type of self-made bone drill applied to percutaneous transforaminal endoscopic discectomy for L5/S1 intervertebral disc herniation.Methods The clinical data of 52 patients with L5/S1 intervertebral disc herniation admitted to our hospital were retrospectively analyzed.All patients underwent percutaneous transforaminal endoscopic discectomy,with a new type of self-made bone drill for foraminoplasty during the surgery.The surgical conditions and occurrence of complications were recorded.The pain of patients before surgery,3 days after surgery,3 months after surgery,6 months after surgery,and 1 year after surgery was assessed by visual analogue scale(VAS);and the neurological function improvement before and after surgery was evaluated by Oswestry disability index(ODI).Results All patients underwent successful surgery without serious complications or recurrence after surgery.The VAS and ODI scores of patients 3 days,3 months,6 months,and 1 year after surgery were significantly lower than those before surgery(P<0.05).Conclusion The self-made new bone drill can significantly improve the efficiency of foraminoplasty and ensure surgical safety,with satisfactory early clinical effect.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

OBJECTIVE: We aimed to assess the feasibility and superiority of machine learning (ML) methods to predict the risk of Major Adverse Cardiovascular Events (MACEs) in chest pain patients with NSTE-ACS. METHODS: Enrolled chest pain patients were from two centers, Beijing Anzhen Emergency Chest Pain Center Beijing Bo'ai Hospital, China Rehabilitation Research Center. Five classifiers were used to develop ML models. Accuracy, Precision, Recall, F-Measure and AUC were used to assess the model performance and prediction effect compared with HEART risk scoring system. Ultimately, ML model constructed by Naïve Bayes was employed to predict the occurrence of MACEs. RESULTS: According to learning metrics, ML models constructed by different classifiers were superior over HEART (History, ECG, Age, Risk factors, & Troponin) scoring system when predicting acute myocardial infarction (AMI) and all-cause death. However, according to ROC curves and AUC, ML model constructed by different classifiers performed better than HEART scoring system only in prediction for AMI. Among the five ML algorithms, Linear support vector machine (SVC), Naïve Bayes and Logistic regression classifiers stood out with all Accuracy, Precision, Recall and F-Measure from 0.8 to 1.0 for predicting any event, AMI, revascularization and all-cause death ( vs. HEART ≤ 0.78), with AUC from 0.88 to 0.98 for predicting any event, AMI and revascularization ( vs. HEART ≤ 0.85). ML model developed by Naïve Bayes predicted that suspected acute coronary syndrome (ACS), abnormal electrocardiogram (ECG), elevated hs-cTn I, sex and smoking were risk factors of MACEs. CONCLUSION Compared with HEART risk scoring system, the superiority of ML method was demonstrated when employing Linear SVC classifier, Naïve Bayes and Logistic. ML method could be a promising method to predict MACEs in chest pain patients with NSTE-ACS.
Humans ; Acute Coronary Syndrome/epidemiology* ; Bayes Theorem ; Feasibility Studies ; Risk Assessment/methods* ; Chest Pain/etiology* ; Myocardial Infarction/diagnosis*

OBJECTIVE: To retrospectively assess the advantages of the modified Uhl technique in the treatment of Colles' fracture guided by the principles of Chinese osteosynthesis (CO) concept. METHODS: A retrospective study was conducted on 358 patients with Colles' fracture treated with the modified Uhl technique of closed reduction and percutaneous pin between January 2016 and June 2021. Out of these, 120 eligible cases were selected and categorized into two groups according to different surgical methods:the closed reduction and percutaneous pin group, and the open reduction group. Sixty-eight patients in the closed reduction and percutaneous pin group were treated with the modified Uhl technique, while fifty-two patients in the open reduction group were treated with open reduction and internal fixation using plates. The modified Sarmiento imaging score, Gartland-Werley wrist score, operation time, hospital stay, and treatment costs between the two groups were compared at a 6-month postoperative follow-up. RESULTS: There were no significant differences in terms of gender, age, affected side, injure factors, time of injury to surgery, Sarmiento imaging score, and Gartland-Werley wrist joint score (P>0.05). The closed reduction and percutaneous pin group exhibited an operation time of (35.88±14.11) minutes, hospitalization stay of (9.78±2.48) days, and treatment costs of (16 074.91±1 964.48) yuan, while the open reduction group demonstrated comparatively longer operation time of (65.48±14.26) minutes, hospitalization stay of (15.88±2.00) days, and treatment costs of (20 451.27±1 760.22) yuan (P<0.01). CONCLUSION The modified Uhl technique presents notable advantages in the management of Colles' fracture, including reliable fixation, less trauma, shorter operation time, less pain, shorter hospital stay, and cost-effectiveness. This technique exhibits promising potential for broader clinical application. However, it is important to note that the pin could potentially damage tendons, and in cases of Colles' fractures with osteoporosis and comminuted fragments, additional techniques may be required for reliable fixation.
Humans ; Retrospective Studies ; Colles' Fracture/surgery* ; Fracture Fixation, Internal ; Fractures, Comminuted ; Hospitalization

Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.

Objective:To explore the medication safety issues caused by unreasonable sugar-to-fat ratio in clinical practice of parenteral nutrition,providing a basis for the rational use of clinical nutritional drugs.Methods:From the beginning of the database construction until February 28,2023,relevant databases at home and abroad were searched to summarize and analyze the clinical adverse outcomes caused by unreasonable sugar-to-fat ratio prescriptions encountered in the included literature and clinical practice.Results:Eleven articles were included,and 1 case of patient discomfort was improved by adjusting the unreasonable sugar-to-fat ratio.A total of 86 patients were involved,including 51 males and 35 females,with an age range of 18 to 89 years.Among the 86 patients,there were 79 clinical adverse outcomes,including 8 deaths.The incidence rates of clinical adverse outcomes were as follows:abnormal liver function 46.8％(37/79),bile stasis 22.8％(18/79),fat overload syndrome 13.9％(11/79),liver steatosis 11.4％(9/79),platelet reduction 3.8％(3/79),and other 1.3％(1/79).Among the 86 patients,2 cases were clearly recorded to have improved clinical adverse outcomes after adjusting the sugar-to-fat ratio,and the others were not detailed.Conclusions:Inappropriate sugar-to-fat ratio may lead to safety issues related to parenteral nutrition medication and should be given clinical attention.